Poor R-wave progression and all-cause mortality in adults without coronary artery disease

Background: Poor R-wave progression (PRWP) on the 12-lead electrocardiogram has been linked to adverse outcomes. Its prognostic value in a contemporary, multi-ethnic population without baseline coronary artery disease (CAD) is unclear. Methods: We analyzed 6,323 adults (mean age 61.9 +- 10.2 years; 54% women) from the Multi-Ethnic Study of Atherosclerosis after excluding pre-excitation, major conduction disease, Q-wave infarction, and missing covariates. PRWP was defined as R-wave amplitude <= 3 mm in V3 with RV3>RV2 and was present in 202 participants (3.2%). Outcomes were all-cause mortality, cardiovascular (CV) death, and major adverse cardiovascular events (MACE: nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke). Cox models adjusted for age, sex, race/ethnicity, hypertension, and diabetes. Results: Over a median 14.1 years (IQR, 13.5-14.7), 1,138 deaths, 256 CV deaths, and 515 MACE occurred. Among PRWP participants, there were 52 deaths (25.7%), 8 CV deaths (4.0%), and 16 MACE (7.9%). In prespecified models, PRWP was not associated with CV death (hazard ratio [HR] 0.87; 95% CI, 0.43-1.76; P=0.690) or MACE (HR 0.94; 95% CI, 0.57-1.54; P=0.796) and showed a borderline association with all-cause mortality (HR 1.31; 95% CI, 0.99-1.73; P=0.059), driven by non-CV deaths. Adjustment for smoking and emphysema attenuated estimates (all-cause HR 1.19; 95% CI, 0.90-1.58; P=0.229). A PRWP x sex interaction was significant for MACE (likelihood-ratio test P=0.002), driven by higher stroke incidence in women; interactions by race/ethnicity were not significant. Conclusions: In a large, CAD-free, multi-ethnic cohort, isolated PRWP was uncommon and did not confer independent risk for CV death or MACE over 14 years. The borderline excess in all-cause mortality was non-CV and diminished after accounting for smoking and emphysema.